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Posts Tagged ‘tpa vs streptokinase’

We know  streptokinase  is a non fibrin specific   agent that   results in systemic lytic state and hence more chance of bleeding.

TPA is fibrin specific  and it  will act only on fibrin  bound to clot , hence systemic bleeding risk should be less.

However , in real world , it is well  documented  stroke risk with TPA is consistently more than streptokinase .(It varies between .0.3-.5% with streptokinase , 0.7-to 1%  with TPA)

How do you explain this apparent  paradox ?

Possible explanations.

  1. The fibrin selectivity pf TPA is not absolute* .
  2. The lytic power of  TPA is more hence stroke is more likely.
  3. The FDP* released by TPA can trigger a systemic lytic state
  4. In the  post TPA protocol   heparin  is  mandatory and  this  contribute to stroke risk.

*What happens o fibrin degradation products (FDP) levels after TPA ?

FDP levels do increase after TPA  .This peaks at 1 hour after lysis.it Correlates well with risk of stroke.(Ho CH, Wang infarction.Thrombosis Research ).

Reference

This is an excellent review with analysis from 14 studies with total of 142 907 patients with thrombolysis

A meta  analysis of thrombolytic agents streptokinase vs tpa tnktpa  stroke risk fibrin slectivity

Ho CH, Wang SP Serial thrombolysis-related changes after thrombolytic therapy with TPA in patients with acute myocardial infarction.Thrombosis Research

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Thrombolytic therapy was a  mini revolution  when it was introduced two decades ago .It has since evolved  , not only in the  molecular structure  but also in it’s usage pattern.

The first generation streptokinase is continued to be used even today  . While the latest generation thrombolytic agent TNKTPA(Tenekteplase) is threatening  to push the  old warrior out of  CCU.

(Of course the  American Physician & Pharma  community  never  gave the due respect to  streptokinase  !)

The two common indications  for thrombolytic therapy  are

  • STEMI
  • Acute pulmonary embolism

Uncommon indications

  • Stroke( Can be common in few institutions)
  • Prosthetic valve thrombosis
  • Rarely DVT

From the beginning , there has been a controversy  about the thrombolytic  dosage and  the speed with which it is to be administered .Let us recall , streptokinase was initially  used  in  various regimes ( 5-30lakh units between a 10 -3hr infusion )  Later ,we arrived at a consensus at  15L units  in 1 hr infusion . TPA also experienced the same . Which  settled  for front loaded regimen(35 + 65mg)  . The confusion reappeared when we developed bolus thrombolytic agents( TNKTPA) .

In STEMI thrombus formation  is  often a one time process  while thrombolysis is a continuous process. In pulmonary embolism both  thrombus formation  and lysis  is often continuous process  .

The success of thrombolysis depends on the sustained  drug concentration ,  the pressure at which the drug interacts  the thrombus.

Many times it is prudent to administer  intensive heparin after thrombolysis  to prevent recurrent thrombosis. Further ,  most of the pulmonary embolisms  will require long term anticoagulants.

How to maximize the success of thrombolytic agents ?

  • Local catheter based thrombolysis can be tried  within the coronary ostium (Largely unpopular)
  • Within the pulmonary artery for pulmonary embolism (Still considered an useful option )

It  makes sense , to administer these thrombolytic agents over a prolonged period of time so that the lytic process gets wider recruitment of the natural lytic mechanisms.

When a drug is infused continuously , the drug  reach the thrombus in  a pulsatile manner , which facilitates thrombus dessication  (Like drip irrigation ) . A long acting drug even with a high concentration may not be  very effective , since  the  drug is required to produce a mechanical effect  here . (Unlike say a long acting antibiotics !)

TPA in Pulmonary embolism

The inadequacies  of  2 hour infusion of TPA is  glaring in acute pulmonary embolism .We believe   a 48-72 hour streptokinase infusion   has a definte edge   over a short and brief TPA infusion.

Issues need answer

It is yet , not understood why we can’ t infuse TPA as  a   long term infusion like streptokinase .

Advantage  of bolus TNK TPA  in  pre-hospital phase of STEMI

The argument in favor of bolus dose  thrombolytic agent  is  the ease of administration .

The other the major advantage claimed  is ,  a 10 second  TNK TPA   in STEMI  can  substantially  reduce the time window   and facilitate  early completion of thrombolysis .

Counter point

But , the  later concept is hard to prove  . . .

In fact , there  are  no controlled studies  available for assessing the   efficacy of TNK-TPA   vs  Streptokinase   with reference to various time windows. We presume so many things. An  incomplete   early thrombolysis  may not be better than a  more  successful  but  slightly delayed TIMI3 flow .

As scientists,  when  we try  to answer these  question we  ask for data .  Are we getting it any way ?  Are the existing data reflect  fact ?     We  wonder,  will we may never get   an  hourly  angiographic  data base  about the IRA  patency  in  TPA bolus  vs streptokinase infusion .

It is most unfortunate,   with  many of the critical questions   still to be answered ,  the cardiology community believes ,  they  have  reached the  summit  of  knowledge  about thrombolytic therapy . Current perception is , the research on  existing  thrombolytic drugs  is  deemed to have been complete .

In this hyped  era of interventional coronary  care  ,   it is a remote possibility   to have any  further comparative studies on thrombolytic agents .

The greatest threat faced by  us  today  is the destiny  of  modern medicine is   often  decided in  few corporate board rooms  and   hence   research questions  rarely  emanate from bed side !

In this scenario, where we are not likely to generate   genuine  clinical  data ,  the only way to move   forward is   to go  by  our experience – ” Genuine  experience to be precise . . .”

Final message

Ease of administration should never be the criteria in choosing a thrombolytic agent . It   can severely    compromise the quality of thrombolysis  ! especially in pulmonary embolism and to a certain extent in STEMI.  Success   rarely  comes  with ease  . . .

Many believe , the choice  between  streptokinase   & TPA    goes much beyond it’s academic reasons.  TNK TPA (Tenektepalse) has come in a big way to replace streptokinase  even   in developing countries.  Ofcourse it is backed by a huge study  ! (ASSENT) .

The cost effectiveness and worthiness  of TPA over streptokinase  was  never proved comprehensively.

Note of caution :

The observation made above is   based on personal  opinion  in  about   20 patients  . Readers are  argued to do their own  analysis on this issue and come to a conclusion .

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